Oh man, this is a tough one. Trigun is my most favorite anime ever, but some of that has to do with nostalgia and warm associations. Gintama is definitely creeping up there, too. But then there's Cowboy Bebop, and Miyazaki films, and Millenium Actress....in the end, I think it might depend on what genre of anime we're talking about, and whether we're talking about personal preference or in some kind of objective sense.